Practice question

Necessity of sonic hedgehog signaling for limb outgrowth and anteroposterior patterning was demonstrated through pharmacologic and genetic inhibition approaches. Treatment with cyclopamine blocking Smoothened signal transduction or Shh-null mouse embryos exhibited severely truncated limbs lacking posterior digits 3-5 and premature downregulation of Gremlin1 resulting in increased BMP activity that represses apical ridge FGF expression. Blocking retinoic acid synthesis shifts axial boundaries, ridge removal tests maintenance, Tbx5 overexpression alters identity, but specific SHH inhibition uniquely reveals dual requirement for growth and patterning in tetrapod limbs.